(±)-2-Hexanol and (±)-2-Heptanol are important fragrance compounds as the S enantiomer of 2-Hexanol possess Mushroom, green, ripe, berry, astringent, metallic odour while R enantiomer of 2-Hexanol possess Mushroom, dusty, oily odour. R-2-Heptanol has Fruity, sweet, oily, fatty odour while S-2-Heptanol has Mushroom, oily, fatty, blue cheese, mouldy odour.
R-(−)-2-Hexanol and S-(+)-2-Hexanol were used in preparation of some of the key intermediates in the total synthesis of antivirally active glycolipid cycloviracin B1.

While R-(−)-2-heptanol is used in resolving the diastereoisomeric mixture of a key intermediate in the synthesis of 1-(2-chloro-4-pyrrolidin-1-ylbenzoyl)-2,3,4,5-tetrahydro-1H-1-benzdiazepine, known to be a strong vasopressin V2 receptor agonist.

(±)-Lavandulol is an important terpene constituent in plants and has also been found in insects. It is chemically known as 2-isopropylpentyl-5-methyl-4-hexen-1-ol, and is represented by the structural formula as shown below.

(±)-Lavandulol and its simple esters, are minor, but important constituents of essential oils. These are common ingredients in the cosmetic industry. The (R)-form is a constituent of French lavender oil, which is used in the perfume chemistry. The fragrance of the nature identical (R)-enantiomer (‘weak floral, herbal odor with slightly lemon-like, fresh citrus fruity nuance’) was superior to those of both the unnatural (S)-enantiomer (‘very weak odor’) and the racemate (‘weak floral, herbal odor’).
Recently, (R)-lavandulol and the different esters of this enantiomer have been identified as sex or aggregation pheromone components in several insects. (R)-Lavandulyl (S)-methylbutanoate is a component of the female sex pheromone of the hibiscus mealybug, (R)-lavandulyl acetate is a component of the male produced sex pheromone of the western flower thrips and (R)-lavandulol is a component of the aggregation pheromone of the strawberry blossom weevil.
Commercially available lavandulol and its acetates are in racemic mixture form. Easy access to the two lavandulol enantiomers is of importance in perfumery because they may display different pharmacological activities and certainly different fragrances and odor thresholds. Therefore, much effort has been made in the synthesis of racemic and chiral lavandulol.
(±)-1-Phenyl ethanol is an important molecule which is used as chiral building block and synthetic intermediates in chemical and pharmaceutical industries. (R)-(+)-1Phenyl ethanol is used as fragrance in cosmetic industry due to mild floral odour and also is used in the preparation of Solvatochromic dye, ophthalmic preservative and inhibitor of cholesterol intestinal adsorption.
(±)-1-Phenyl propanol is also used as flavor and chloeretic agent in cosmetic and pharmaceutical industry.
Oritani, T. et al. (Agr. Biol. Chem. 1973, 37, 1923-1928) describe that microbial asymmetrical hydrolysis of the acetates of the racemic prim-alcohols having an asymmetrical carbon atom at the ß-position gave lower optically active alcohols and the acetates of their antipodes using microorganisms (Bacillus subtilis var. Niger, Trichoderma S).
An article by Kenji Mori describes the preparative scale enantioselective oxidation of 1,3-dithiane to the corresponding monosulfoxide using whole-cell cultures of two bacteria, i.e. Acinetobactercalcoaceticus NCIMB 9871 and Pseudomonas sp. NCIMB 9872 (Tetrahedron Letters; Volume 37, Issue 34, 19 Aug. 1996, Pages 6117-6120; doi:10.1016/0040-4039(96)01306-8; Microbiological transformations 35).
There are some of the recent developments in the rapidly growing field of lipase-catalyzed kinetic resolution of racemates for the separation of enantiomers in presence of biocatalyst (enzyme or a microorganism) or a chemocatalyst (chiral acid or base or even a chiral metal complex). Asymmetric hydrolysis of the racemic binaphthyldibutyrate (the ester) using whole cells from bacteria species afforded the (R)-diol with 96% ee and the unreacted substrate (S)-ester with 94% ee at 50% conversion (Ashraf Ghanem and Hassan Y. Aboul-Enein; Chirality 17:1-15, 2005). According to Thomas Daufßmannetal.biocatalytic processes are useful methods for the production of chiral intermediates (chiral alcohol). Biological systems such as whole cell biotransformations with yeast are applied. Recently, enzymatic processes using whole cell fermentation or isolated alcohol dehydrogenases (ADHs) have gained increased interest for the commercial production of chiral alcohols (Engineering in Life Sciences; Volume 6 Issue 2, Pages 125-129; DOI: 10.1002/elsc. 200620910).
Mori et al. used the diastereoselective alkylation of the chiral 3-hydroxy ester as key step for the synthesis of (S)-Lavandulol and (S)-Citronellol. Alternatively, biocatalytic reduction of (3-keto esters) in whole cell processes with bakers' yeast was used.
Hannah Cros et al. describe asymmetric esterification of the racemic primary alcohol lavandulol using lipase B from Candida antarctica and acetic acid as acyl donor in 80% yield. The enantioselectivity of the process was characterized, and a preparative resolution of 25 mm racemic lavandulol, stopped at approx. 55% conversion, yielded (S)-lavandulol and (R)-lavandulyl acetate (Hannah Cros et al; Biotechnology Letters; Springer Netherlands; Volume 26, Number 5/March, 2004; DOI:10.1023/B:BILE. 0000018268. 42802.d0; pp 457-460)
AnatZada et al. report the preparation of the two enantiomers of lavandulol and lavandulylsenecioate, starting from racemic lavandulol based on a two-cycle enzymatic transesterification of racemic lavandulol with vinyl acetate using Porcine pancreas lipase. High enantioselectivity was achieved while the preparation yielded (R)-lavandulol with 96.7% ee and (S)-lavandulol with 92.6% ee (Tetrahedron: Asymmetry; Volume 15, Issue 15, 9 Aug. 2004, Pages 2339-2343; doi:10.1016/j.tetasy.2004.06.015). The drawback of the method is the need of lengthy column chromatography in order to separate the unreacted alcohol from the formed acetate.
Further, AnatZada et al. describe a convenient resolution of racemic lavandulol through lipase-catalyzed acylation with succinic anhydride. Porcine pancreas lipase from Sigma or Hog pancreas lipase from Fluka were chosen on the basis of previous screening of different lipases for the resolution of (±)-lavandulol. This method is used for the preparation of enantiomerically pure (R)-lavandulol with 98% ee in one resolution cycle. The (S)-lavandulol with 90% ee can be obtained by a second resolution cycle (Tetrahedron: Asymmetry; Volume 17, Issue 2, 23 Jan. 2006, Pages 230-233; doi:10.1016/j.tetasy.2005.12.021). This process has limitation for the large scale production.
According to Teresa Olsen et al. monoterpenelavandulol has been successfully converted to lavandulyl acetate by enzymatic catalysis in supercritical carbon dioxide using immobilized Candida antarctica lipase B (Novozym 435). Conversions of up to 86% were observed at substrate concentrations of 60 mM at 60° C. and 10 MPa. Increased temperature of the system resulted in lower enantioselectivity, whereas changes in pressure/density had little effect on this parameter (Enzyme and Microbial Technology; Volume 39, Issue 4, 2 Aug. 2006, Pages 621-625; doi:10.1016/j.enzmictec.2005.11.025).
EP 0258666 (A2) relates to the stereoselective transformation of alcohol substrate (lavandulol and analogous alcohols) to the corresponding acid (lavandulic acid) by oxidizing enzymes originating from microorganisms (disclosed three species of Aspergillus genus i.e. Aspergillusochraceus (ATCC 18500); Aspergillusflavipes (ATCC 1030); and Aspergillusflavipes (ATCC 11013). These microorganisms contain one or more enzymes which transform the alcohols to the corresponding acid, perhaps as a detoxification mechanism.
In “A convenient resolution of racemic lavandulol through lipase-catalyzed acylation with succinic anhydride: simple preparation of enantiomerically pure (R)-lavandulol” by Anat Zada and Ezra Dunkelblum; Tetrahedron: Asymmetry; Volume 17, Issue 2, 23 Jan. 2006, Pages 230-233, where a commercial Porcine pancreatic lipase is used for converting (±)-Lavandulol to its S-Lavandulol acetate with succinic acid as an Acyl donor in organic solvent.
In our case we have used (±)-Lavandulol acetate as a precursor which when incubated with fungus F. Proliferatum gives R-Lavandulol as final product with >95% e.e. Based on the results obtained from GC chromatograms we are predicting involvement of two enzyme systems involved in catalyzing the same reaction. Where first (±)-Lavandulyl acetate is deacylated to form (±)-Lavandulol and then another probable enzyme alcohol Dehydrogenase catalyses conversion of (±)-Lavandulol to R-(−)-Lavandulol. Since our fungal system catalyses conversion of (±)-Lavandulyl acetate to R-Lavandulol in aqueous system rather than in organic solvent as mentioned in prior art. It has advantage of scaling it in large scale fermenter level as whole cells are used over the conventional use of pure enzymes. Use of pure enzymes increase the cost of production over whole cell method as no costly cofactors are needed in this process and enzyme recovery is very low. So the process mentioned by us shows an advantage over that mentioned in prior art.
There is an urgent need of a process for preparing enantiomerically pure (R)-alcohols which is cost effective, simple, and will be useful for the production of (R)-alcohol commercially in large scale.